Project Background/Rationale. Alzheimer's disease (AD) afflicts nearly 6 million Americans, a number projected to grow in coming decades. AD is known to have a long preclinical phase in which pathophysiologic processes develop many years, even decades, before the onset of clinical symptoms. During this preclinical phase there is evidence of unremitting decline in cognitive function, particularly in episodic memory. Thus far, evidence of the efficacy of pharmacological interventions to slow this decline in cognitive function has been limited, leading to increasing interest in the utility of nonpharmacological interventions including exercise. Project Objectives. We propose to assess the feasibility of a novel home-based exercise intervention to improve episodic memory that uses resistance training coupled with real-time guidance delivered remotely in 60 individuals 50 years of age or older with mild cognitive impairment. Preliminary data on outcome measures (Rey-Osterrieth Complex Figure Test, Wechsler Logical Memory Test), a potential mediator (insulin-like growth factor-1), and a potential moderator (apolipoprotein E?4) will be obtained. Project Methods. We will estimate the difference between the intervention (n=30) and the control group (n=30) on 6-month change in episodic memory (Rey-Osterrieth Complex Figure Test, Wechsler Logical Memory Test) as well as the effect size, which will be used as a basis for sample size calculation for a proposed larger study. In addition, we will explore 6-month change in serum insulin-like growth factor-1 concentration during the resistance exercise program as a potential mediator of exercise-related changes in episodic memory. Further, we will explore apolipoprotein E?4 carrier status (carrier/noncarrier) as a potential moderator.